Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study

Leo, Paul J., Madeleine, Margaret M., Wang, Sophia, Schwartz, Stephen M., Newell, Felicity, Pettersson-Kymmer, Ulrika, Hemminki, Kari, Hallmans, Goran, Tiews, Sven, Steinberg, Winfried, Rader, Janet S., Castro, Felipe, Safaeian, Mahboobeh, Franco, Eduardo L., Coutlee, Francois, Ohlsson, Claes, Cortes, Adrian, Marshall, Mhairi, Mukhopadhyay, Pamela, Cremin, Katie, Johnson, Lisa G., Garland, Suzanne, Tabrizi, Sepehr N., Wentzensen, Nicolas, Sitas, Freddy, Little, Julian, Cruickshank, Maggie, Frazer, Ian H., Hildesheim, Allan and Brown, Matthew A. (2017) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. Plos Genetics, 13 8: e1006866. doi:10.1371/journal.pgen.1006866

Author Leo, Paul J.
Madeleine, Margaret M.
Wang, Sophia
Schwartz, Stephen M.
Newell, Felicity
Pettersson-Kymmer, Ulrika
Hemminki, Kari
Hallmans, Goran
Tiews, Sven
Steinberg, Winfried
Rader, Janet S.
Castro, Felipe
Safaeian, Mahboobeh
Franco, Eduardo L.
Coutlee, Francois
Ohlsson, Claes
Cortes, Adrian
Marshall, Mhairi
Mukhopadhyay, Pamela
Cremin, Katie
Johnson, Lisa G.
Garland, Suzanne
Tabrizi, Sepehr N.
Wentzensen, Nicolas
Sitas, Freddy
Little, Julian
Cruickshank, Maggie
Frazer, Ian H.
Hildesheim, Allan
Brown, Matthew A.
Title Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study
Journal name Plos Genetics   Check publisher's open access policy
ISSN 1553-7404
Publication date 2017-08-01
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1006866
Open Access Status DOI
Volume 13
Issue 8
Start page e1006866
Total pages 20
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1105 Ecology, Evolution, Behavior and Systematics
1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
1306 Cancer Research
Abstract A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
Keyword Human-Papillomavirus Infection
Squamous-Cell Carcinoma
Comprehensive Analysis
Familial Risks
Complex Traits
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 001
P01 CA042792
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Faculty of Medicine
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